Dyspnea (shortness of breath) is a leading symptom of both cardiovascular and pulmonary disease. It is severely distressing and debilitating. Dyspnea is as common as pain in patients hospitalized for serious disease and is also very prevalent in outpatients. Despite its prevalence and associated suffering, there is surprisingly little known about neurophysiology and perception of dyspnea, especially when compared to pain. Our goal is to improve basic understanding of perceptual mechanisms by test the hypothesis that the perception of dyspnea comprises sensory and affective dimensions that can be discriminated and modulated separately and that must be measured jointly to adequately characterize the symptom. Existing general dyspnea measures do not address the concept of multiple dimensions of dyspnea. There is a useful and widely accepted model of pain as a multidimensional experience. Evidence shows that some aspects of that model apply to dyspnea, e.g., characterization of the sensory dimension as consisting of qualitatively distinguishable sensations. A multi-stage affective dimension model comprising stages of immediate unpleasantness (how 'bad' it feels now) and consequent emotional/evaluative responses (how 'scary' or 'depressing1 it is) has never been tested for dyspnea. We will test whether this conceptual model applies to dyspnea in 3 studies designed to have congruent aims, hypotheses, and measurements across a spectrum of settings and conditions: 1) dyspnea induced by controlled laboratory methods in both healthy subjects and patients; 2) current dyspnea in patients of differing diagnoses in the emergency department; and 3) changes in dyspnea in COPD patients undergoing a therapeutic exercise program. Members of our interdisciplinary team have made substantial contributions to the understanding and measurement of sensory components of dyspnea and determination of neural mechanisms. Our findings have led us to focus this proposal on conceptual clarification of the affective dimension. We will examine the relationships between the affective stages of immediate unpleasantness and emotional response and the sensory dimension (intensity and quality). Our goal is to clarify the aspects of dyspnea that are important in various clinical and laboratory settings. We believe a better conceptual model of the dimensions of dyspnea will lead to improved methods of measurement, selection of more relevant laboratory models, better assessment of interventions in clinical trials, and better translation between laboratory work and clinical studies. [unreadable] [unreadable] [unreadable]